GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer

Paul D P Pharoah; Ya-Yu Tsai; Susan J Ramus; Catherine M Phelan; Ellen L Goode; Kate Lawrenson; Melissa Buckley; Brooke L Fridley; Jonathan P Tyrer; Howard Shen; Rachel Weber; Rod Karevan; Melissa C Larson; Honglin Song; Daniel C Tessier; François Bacot; Daniel Vincent; Julie M Cunningham; Joe Dennis; Ed Dicks; Katja K Aben; Hoda Anton-Culver; Natalia Antonenkova; Sebastian M Armasu; Laura Baglietto; Elisa V Bandera; Matthias W Beckmann; Michael J Birrer; Greg Bloom; Natalia Bogdanova; James D Brenton; Louise A Brinton; Angela Brooks-Wilson; Robert James (Jim) Brown; Ralf Butzow; Ian Campbell; Michael E Carney; Renato S Carvalho; Jenny Chang-Claude; Y Anne Chen; Zhihua Chen; Wong-Ho Chow; Mine S Cicek; Gerhard Coetzee; Linda S Cook; Estrid Høgdall; Claus K Høgdall; Allan Jensen; Susanne Krüger Kjaer; Lene Lundvall; Australian Cancer Study

doi:10.1038/ng.2564

GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer

Paul D P Pharoah, Ya-Yu Tsai, Susan J Ramus, Catherine M Phelan, Ellen L Goode, Kate Lawrenson, Melissa Buckley, Brooke L Fridley, Jonathan P Tyrer, Howard Shen, Rachel Weber, Rod Karevan, Melissa C Larson, Honglin Song, Daniel C Tessier, François Bacot, Daniel Vincent, Julie M Cunningham, Joe Dennis, Ed DicksKatja K Aben, Hoda Anton-Culver, Natalia Antonenkova, Sebastian M Armasu, Laura Baglietto, Elisa V Bandera, Matthias W Beckmann, Michael J Birrer, Greg Bloom, Natalia Bogdanova, James D Brenton, Louise A Brinton, Angela Brooks-Wilson, Robert James (Jim) Brown, Ralf Butzow, Ian Campbell, Michael E Carney, Renato S Carvalho, Jenny Chang-Claude, Y Anne Chen, Zhihua Chen, Wong-Ho Chow, Mine S Cicek, Gerhard Coetzee, Linda S Cook, Estrid Høgdall, Claus K Høgdall, Allan Jensen, Susanne Krüger Kjaer, Lene Lundvall, Australian Cancer Study

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304 Citationer (Scopus)

Abstract

Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC), with another two suggestive loci reaching near genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the UK. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. We performed follow-up genotyping in 18,174 individuals with EOC (cases) and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 that were previously found to have associations close to genome-wide significance and identified three loci newly associated with risk: two loci associated with all EOC subtypes at 8q21 (rs11782652, P = 5.5 × 10(-9)) and 10p12 (rs1243180, P = 1.8 × 10(-8)) and another locus specific to the serous subtype at 17q12 (rs757210, P = 8.1 × 10(-10)). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility and implicated CHMP4C in the pathogenesis of ovarian cancer.

Originalsprog	Engelsk
Tidsskrift	Nature Genetics
Vol/bind	45
Udgave nummer	4
Sider (fra-til)	362-70, 370e1-2
ISSN	1061-4036
DOI	https://doi.org/10.1038/ng.2564
Status	Udgivet - apr. 2013

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10.1038/ng.2564

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3693183/pdf/nihms-474884.pdf

Citationsformater

Pharoah, P. D. P., Tsai, Y.-Y., Ramus, S. J., Phelan, C. M., Goode, E. L., Lawrenson, K., Buckley, M., Fridley, B. L., Tyrer, J. P., Shen, H., Weber, R., Karevan, R., Larson, M. C., Song, H., Tessier, D. C., Bacot, F., Vincent, D., Cunningham, J. M., Dennis, J., ... Australian Cancer Study (2013). GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer. Nature Genetics, 45(4), 362-70, 370e1-2. https://doi.org/10.1038/ng.2564

Pharoah, PDP, Tsai, Y-Y, Ramus, SJ, Phelan, CM, Goode, EL, Lawrenson, K, Buckley, M, Fridley, BL, Tyrer, JP, Shen, H, Weber, R, Karevan, R, Larson, MC, Song, H, Tessier, DC, Bacot, F, Vincent, D, Cunningham, JM, Dennis, J, Dicks, E, Aben, KK, Anton-Culver, H, Antonenkova, N, Armasu, SM, Baglietto, L, Bandera, EV, Beckmann, MW, Birrer, MJ, Bloom, G, Bogdanova, N, Brenton, JD, Brinton, LA, Brooks-Wilson, A, Brown, RJ, Butzow, R, Campbell, I, Carney, ME, Carvalho, RS, Chang-Claude, J, Chen, YA, Chen, Z, Chow, W-H, Cicek, MS, Coetzee, G, Cook, LS, Høgdall, E , Høgdall, CK, Jensen, A, Kjaer, SK, Lundvall, L & Australian Cancer Study 2013, 'GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer', Nature Genetics, bind 45, nr. 4, s. 362-70, 370e1-2. https://doi.org/10.1038/ng.2564

@article{fca77a6233f94ce19258b75f965d1ac1,

title = "GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer",

abstract = "Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC), with another two suggestive loci reaching near genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the UK. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. We performed follow-up genotyping in 18,174 individuals with EOC (cases) and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 that were previously found to have associations close to genome-wide significance and identified three loci newly associated with risk: two loci associated with all EOC subtypes at 8q21 (rs11782652, P = 5.5 × 10(-9)) and 10p12 (rs1243180, P = 1.8 × 10(-8)) and another locus specific to the serous subtype at 17q12 (rs757210, P = 8.1 × 10(-10)). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility and implicated CHMP4C in the pathogenesis of ovarian cancer.",

keywords = "Case-Control Studies, Cooperative Behavior, Cystadenocarcinoma, Serous, Female, Gene-Environment Interaction, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Meta-Analysis as Topic, Neoplasm Invasiveness, Ovarian Neoplasms, Polymorphism, Single Nucleotide, Risk Factors",

author = "Pharoah, {Paul D P} and Ya-Yu Tsai and Ramus, {Susan J} and Phelan, {Catherine M} and Goode, {Ellen L} and Kate Lawrenson and Melissa Buckley and Fridley, {Brooke L} and Tyrer, {Jonathan P} and Howard Shen and Rachel Weber and Rod Karevan and Larson, {Melissa C} and Honglin Song and Tessier, {Daniel C} and Fran{\c c}ois Bacot and Daniel Vincent and Cunningham, {Julie M} and Joe Dennis and Ed Dicks and Aben, {Katja K} and Hoda Anton-Culver and Natalia Antonenkova and Armasu, {Sebastian M} and Laura Baglietto and Bandera, {Elisa V} and Beckmann, {Matthias W} and Birrer, {Michael J} and Greg Bloom and Natalia Bogdanova and Brenton, {James D} and Brinton, {Louise A} and Angela Brooks-Wilson and Brown, {Robert James (Jim)} and Ralf Butzow and Ian Campbell and Carney, {Michael E} and Carvalho, {Renato S} and Jenny Chang-Claude and Chen, {Y Anne} and Zhihua Chen and Wong-Ho Chow and Cicek, {Mine S} and Gerhard Coetzee and Cook, {Linda S} and Estrid H{\o}gdall and H{\o}gdall, {Claus K} and Allan Jensen and Kjaer, {Susanne Kr{\"u}ger} and Lene Lundvall and {Australian Cancer Study}",

year = "2013",

month = apr,

doi = "10.1038/ng.2564",

language = "English",

volume = "45",

pages = "362--70, 370e1--2",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "4",

}

TY - JOUR

T1 - GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer

AU - Pharoah, Paul D P

AU - Tsai, Ya-Yu

AU - Ramus, Susan J

AU - Phelan, Catherine M

AU - Goode, Ellen L

AU - Lawrenson, Kate

AU - Buckley, Melissa

AU - Fridley, Brooke L

AU - Tyrer, Jonathan P

AU - Shen, Howard

AU - Weber, Rachel

AU - Karevan, Rod

AU - Larson, Melissa C

AU - Song, Honglin

AU - Tessier, Daniel C

AU - Bacot, François

AU - Vincent, Daniel

AU - Cunningham, Julie M

AU - Dennis, Joe

AU - Dicks, Ed

AU - Aben, Katja K

AU - Anton-Culver, Hoda

AU - Antonenkova, Natalia

AU - Armasu, Sebastian M

AU - Baglietto, Laura

AU - Bandera, Elisa V

AU - Beckmann, Matthias W

AU - Birrer, Michael J

AU - Bloom, Greg

AU - Bogdanova, Natalia

AU - Brenton, James D

AU - Brinton, Louise A

AU - Brooks-Wilson, Angela

AU - Brown, Robert James (Jim)

AU - Butzow, Ralf

AU - Campbell, Ian

AU - Carney, Michael E

AU - Carvalho, Renato S

AU - Chang-Claude, Jenny

AU - Chen, Y Anne

AU - Chen, Zhihua

AU - Chow, Wong-Ho

AU - Cicek, Mine S

AU - Coetzee, Gerhard

AU - Cook, Linda S

AU - Høgdall, Estrid

AU - Høgdall, Claus K

AU - Jensen, Allan

AU - Kjaer, Susanne Krüger

AU - Lundvall, Lene

AU - Australian Cancer Study

PY - 2013/4

Y1 - 2013/4

N2 - Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC), with another two suggestive loci reaching near genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the UK. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. We performed follow-up genotyping in 18,174 individuals with EOC (cases) and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 that were previously found to have associations close to genome-wide significance and identified three loci newly associated with risk: two loci associated with all EOC subtypes at 8q21 (rs11782652, P = 5.5 × 10(-9)) and 10p12 (rs1243180, P = 1.8 × 10(-8)) and another locus specific to the serous subtype at 17q12 (rs757210, P = 8.1 × 10(-10)). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility and implicated CHMP4C in the pathogenesis of ovarian cancer.

AB - Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC), with another two suggestive loci reaching near genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the UK. We selected the top 24,551 SNPs for inclusion on the iCOGS custom genotyping array. We performed follow-up genotyping in 18,174 individuals with EOC (cases) and 26,134 controls from 43 studies from the Ovarian Cancer Association Consortium. We validated the two loci at 3q25 and 17q21 that were previously found to have associations close to genome-wide significance and identified three loci newly associated with risk: two loci associated with all EOC subtypes at 8q21 (rs11782652, P = 5.5 × 10(-9)) and 10p12 (rs1243180, P = 1.8 × 10(-8)) and another locus specific to the serous subtype at 17q12 (rs757210, P = 8.1 × 10(-10)). An integrated molecular analysis of genes and regulatory regions at these loci provided evidence for functional mechanisms underlying susceptibility and implicated CHMP4C in the pathogenesis of ovarian cancer.

KW - Case-Control Studies

KW - Cooperative Behavior

KW - Cystadenocarcinoma, Serous

KW - Female

KW - Gene-Environment Interaction

KW - Genetic Loci

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Genotype

KW - Humans

KW - Meta-Analysis as Topic

KW - Neoplasm Invasiveness

KW - Ovarian Neoplasms

KW - Polymorphism, Single Nucleotide

KW - Risk Factors

U2 - 10.1038/ng.2564

DO - 10.1038/ng.2564

M3 - Journal article

C2 - 23535730

SN - 1061-4036

VL - 45

SP - 362-70, 370e1-2

JO - Nature Genetics

JF - Nature Genetics

IS - 4

ER -

GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer

Abstract

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